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Lipid Phosphate Phosphatase-3 Regulates Tumor Growth via β-catenin and Cyclin-D1 Signaling

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posted on 27.05.2012 by Ishita Chatterjee, Joseph O. Humtsoe, Erin E. Kohler, Claudio Sorio, Kishore K. Wary
Background: The acquisition of proliferative and invasive phenotypes is considered a hallmark of neoplastic transformation; however, the underlying mechanisms are less well known. Lipid phosphate phosphatase-3 (LPP3) not only catalyzes the dephosphorylation of the bioactive lipid sphingosine-1-phosphate (S1P) to generate sphingosine but also may regulate embryonic development and angiogenesis via the Wnt pathway. The goal of this study was to determine the role of LPP3 in tumor cells. Results: We observed increased expression of LPP3 in glioblastoma primary tumors and in U87 and U118 glioblastoma cell lines. We demonstrate that LPP3-knockdown inhibited both U87 and U118 glioblastoma cell proliferation in culture and tumor growth in xenograft assays. Biochemical experiments provided evidence that LPP3-knockdown reduced β-catenin, CYCLIN-D1, and CD133 expression, with a concomitant increase in phosphorylated β-catenin. In a converse experiment, the forced expression of LPP3 in human colon tumor (SW480) cells potentiated tumor growth via increased β-catenin stability and CYCLIN-D1 synthesis. In contrast, elevated expression of LPP3 had no tumorigenic effects on primary cells. Conclusions: These results demonstrate for the first time an unexpected role of LPP3 in regulating glioblastoma progression by amplifying β-catenin and CYCLIN-D1 activities.

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Studies were supported by National Institutes of Health grants (R01HL079356; HL079356-03S1) and by the University of Illinois at Chicago (UIC) Center for Clinical and Translational Science (CCTS) Award Number UL1RR029879, from the National Center for Research Resources, to K.K.W. E.E.K. was supported by National Institutes of Health T32GM070388 and T32HL072742 Training grants.

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Publisher Statement

© 2011 Chatterjee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The original version is available through BioMed Central at DOI: 10.1186/1476-4598-10-51.

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BioMed Central

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en_US

issn

1476-4598

Issue date

11/05/2011

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